Chlamydia trachomatis, an obligate intracellular parasite, is the most common sexually transmitted bacterial pathogen in the world. Infections are often asymptomatic and can cause serious complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. In addition, chlamydial infections may increase the risk of human immunodeficiency virus (HIV) transmission. The development of topical microbicides to prevent sexually transmitted infections has recently gained attention. We have developed the in vitro minimal cidal concentration (MCC) assay to test the direct action of microbicides on the extracellular, infectious chlamydial EBs. We now propose to continue developing the MCC assay by studying the in vitro safety and efficacy of peptide and lipid topical microbicides and the effects of strain variation and the presence of human albumin, simulated vaginal fluid, or simulated semen. The MCC assay will further be employed to analyze the effect of novel antimicrobial agents, placed in formulation with universal placebo singly or in combination, for their activity against C. trachomatis. Finally, we will examine safe and active selected formulations of candidate topical microbicides in vivo in a non-human primate model for vaginal and rectal safety and efficacy. The mode of action of anti-chlamydial microbicides on the organism will be assessed as well as the possibility of C. trachomatis strains developing resistance to the selected microbicides. By providing these highly specialized laboratory tests and expertise not readily available in other laboratories, the chlamydia laboratory will contribute fundamentally to topical microbicide research which will ultimately help to prevent HIV and chlamydial infections around the world. [unreadable] [unreadable] [unreadable]